SOGC CLINICAL PRACTICE GUIDELINE
Venous Thromboembolism and Antithrombotic Therapy in Pregnancy

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Abstract

Objective

To present an approach, based on current evidence, for the diagnosis, treatment, and thromboprophylaxis of venous thromboembolism in pregnancy and postpartum.

Evidence

Published literature was retrieved through searches of PubMed, Medline, CINAHL, and The Cochrane Library from November 2011 to July 2013 using appropriate controlled vocabulary (e.g. pregnancy, venous thromboembolism, deep vein thrombosis, pulmonary embolism, pulmonary thrombosis) and key words (e.g., maternal morbidity, pregnancy complications, thromboprophylaxis, antithrombotic therapy). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies published in English or French. There were no date restrictions. Grey (unpublished) literature was identified through searching the websites of clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies.

Values

The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventative Health Care (Table 1).

Section snippets

Recommendations

  • 1.

    Objective testing is required following clinical suspicion of deep vein thrombosis or pulmonary embolism. (II-2A)

  • 2.

    For the diagnosis of deep vein thrombosis, ultrasonography is recommended, and should be repeated at least once over 7 days if the initial study is negative. For each examination, the entire length of the venous system from the external iliac to the popliteal vein must be visualized and compression manoeuvres performed from the femoral to the popliteal vein. (II-2B)

  • 3.

    For the diagnosis

INTRODUCTION

This guideline summarizes the available data and the quality of the evidence to provide practical approaches to the diagnosis, management, and prevention of VTE in pregnancy. VTE remains an important cause of maternal morbidity and mortality in Canada with an overall incidence of DVT and PE of 12.1 per 10 000 and 5.4 per 10 000 pregnancies, respectively.1 VTE occurs at a rate of 5.4 per 10 000 antepartum, 7.2 per 10 000 peripartum, and 4.3 per 10 000 pregnancies postpartum.1 These rates are

ACUTE VENOUS THROMBOEMBOLISM IN PREGNANCY

Due to hormonal influences on vascular tone and compressive effects on veins by the enlarging uterus, DVT in pregnancy generally presents in the lower extremities, with a predisposition for the left leg (70 to 80%).16., 17. In contrast to their presentation in non-pregnant patients, DVTs are often isolated to the iliac and/or femoral vein during pregnancy (61%).18 Consequently diagnostic approaches advocated for use in non-pregnant patients require modification in pregnancy.8

Setting

Once an acute VTE is confirmed, therapeutic anticoagulation should be instituted promptly. There are no studies confirming the safety of outpatient management in pregnancy for women with acute VTE. Given the additional fetal concerns, pregnant women with an acute PE and/or a large proximal DVT should be considered for hospitalization or followed closely as outpatients in the initial two weeks following diagnosis if they remain hemodynamically stable.

Recommendation

  • 5.

    Pregnant women diagnosed with

CEREBRAL VENOUS THROMBOSIS

The incidence of CVT ranges from 0.01% to 0.04% in Western countries.69 Pregnancy and the puerperium, Caesarean section, dehydration, anemia, thrombophilia, and hypertension are identified risk factors.69., 70., 71. Symptoms and signs include diffuse headache, altered consciousness, seizures, and focal neurological deficits. CT venography and/or MRI studies should be performed in suspected CVT if initial imaging modalities without contrast are negative or inconclusive.

Once CVT is diagnosed,

SUPERFICIAL THROMBOPHLEBITIS

Superficial thrombophlebitis is inflammation with or without thrombosis of a superficial vein, isolated or associated with peripheral or central catheters. The incidence in pregnancy is 0.068%.72 ST is usually self-limiting, but it can extend into the deep venous system and/or recur. Factors associated with DVT include bilateral ST, ST presenting near the deep venous system (saphenofemoral and saphenopopliteal junctions), systemic infection, absence of varicose veins, and a previous history of

OVARIAN VEIN THROMBOSIS

Ovarian vein thrombosis is an uncommon event, complicating 0.05% to 0.18% of pregnancies and affecting the right vein in up to 90% of cases.78., 79. Risk factors include Caesarean section, multiple gestation, and infection.79 Complications include extension of the thrombus into the vena cava and/or renal veins, and sepsis. PE occurs in 13% of cases.80 Symptoms and signs of OVT include nausea, vomiting, guarding, constant lower abdominal or flank pain, palpable sausage-shaped tender abdominal

THROMBOPHILIA SCREENING AFTER THE DIAGNOSIS OF ACUTE VTE

There is no consensus as to whether or not patients require thrombophilia testing following the diagnosis of an acute VTE in the non-pregnant state. The acute management of the current or subsequent pregnancies is generally not altered by knowledge of the thrombophilia status, nor is counselling regarding subsequent risks of VTE. However, patients with VTE and a known family history of PS, PC, or AT deficiency would benefit from screening, as these might affect the duration of anticoagulation

MANAGEMENT OF ANTICOAGULATION THERAPY IN PREGNANT WOMEN WITH MECHANICAL HEART VALVES

For management of anticoagulation therapy in these patients, we would refer clinicians to the guidelines published by American College of Chest Physicians.9

ANTEPARTUM THROMBOPROPHYLAXIS

Recognizing that the pregnant state confers an increased risk for VTE is only the first step in determining which women will benefit from thromboprophylaxis during pregnancy. Although there is a 10-fold increase over baseline, the absolute risk of VTE during pregnancy remains low (0.5 per 1000 pregnancies),1 and LMWH is not a risk-free medication (see Table 2). Hence, the difficulty in clinical practice is reconciling the low absolute risk of VTE with the low risk of side effects associated

ASSISTED REPRODUCTIVE TECHNOLOGY

The risk of VTE in women undergoing ART is estimated to be 0.11% per cycle of in vitro fertilization111; however, in the presence of severe OHSS it is as high as 0.78%.112 Additionally, up to 70% of VTEs in OHSS involve the upper extremity, a much higher incidence than expected.113., 114. VTE associated with ART and OHSS may also present weeks or even months after the resolution of the OHSS.115 There is currently little to guide clinicians in the use of thromboprophylaxis in women undergoing

Management Before Delivery and Neuraxial Anaesthesia

Current consensus guidelines on the use of neuraxial (epidural, spinal, combined spinal/epidural) analgesia or anaesthesia in patients on anticoagulants largely refer to the management of non-obstetric patients.10., 116., 117. Similar recommendations for obstetric patients are extrapolated from recommendations for non-obstetric patients and “weak” evidence (e.g. case reports, case series, pharmacokinetic studies), and do not take into account the physiological changes of pregnancy. These

POSTPARTUM THROMBOPROPHYLAXIS

Postpartum PE is a leading cause of maternal mortality in Canada, with up to 17 maternal deaths each year.125 The “per day” risk is 15- to 35-fold greater in the 6 weeks following delivery than in non-pregnant age-matched control subjects, with the highest risk being in the first 3 weeks.3., 5., 6., 7.

It is generally agreed that universal postpartum thromboprophylaxis is neither cost-effective nor recommended.126., 127. However, an institutional policy on the prevention of postpartum VTE is an

Adverse Pregnancy Conditions: Screening

In the 1990s reports of an increase in placenta-mediated pregnancy complications (e.g. recurrent miscarriage, late fetal loss, preeclampsia, placental abruption, and intrauterine growth restriction) in women with thrombophilia appeared in the literature.141., 142., 143., 144. Whereas these early studies suggested a weak association between inherited thrombophilia and placenta-mediated pregnancy complications, subsequent prospective cohort studies suggested no association between most

FUTURE DIRECTIONS

As we now better understand the appropriate diagnosis of DVT in pregnant women, studies elucidating diagnostic strategies for PE during pregnancy which minimize both fetal and maternal radiation exposure are still required. Even as LMWH replaces UH as the anticoagulant of choice in pregnancy, questions surrounding appropriate dosing regimens or the need for monitoring anti-Xa activity still remain.

As we unequivocally accept that VTE prevention is an important strategy to reduce maternal

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    This clinical practice guideline has been prepared by the VTE in Pregnancy Guideline Working Group, reviewed by Maternal Fetal Medicine and Family Physician Advisory committees and approved by the Executive and Council of the Society of Obstetricians and Gynaecologists of Canada.

    Disclosure statements have been received from all contributors.

    This document reflects emerging clinical scientific advances on the date issued is subject to change. The information should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be reproduced in any form without prior written permission of the SOGC.

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